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KCNQ (K V 7) channels are voltage-gated potassium (K V ) channels, and the function of K V 7 channels in muscles, neurons, and sensory cells is well established. We confirmed that overall blockade of K V  channels with tetraethylammonium augmented the mineralization of bone-marrow-derived human mesenchymal stem cells during osteogenic differentiation, and we determined that K V 7.3 was expressed in MG-63 and Saos-2 cells at the mRNA and protein levels. In addition, functional K V 7 currents were detected in MG-63 cells. Inhibition of K V 7.3 by linopirdine or XE991 increased the matrix mineralization during osteoblast differentiation. This was confirmed by alkaline phosphatase, osteocalcin, and osterix in MG-63 cells, whereas the expression of Runx2 showed no significant change. The extracellular glutamate secreted by osteoblasts was also measured to investigate its effect on MG-63 osteoblast differentiation. Blockade of K V 7.3 promoted the release of glutamate via the phosphorylation of extracellular signal-regulated kinase 1/2-mediated upregulation of synapsin, and induced the deposition of type 1 collagen. However, activation of K V 7.3 by flupirtine did not produce notable changes in matrix mineralization during osteoblast differentiation. These results suggest that K V 7.3 could be a novel regulator in osteoblast differentiation.

The Role of KV7.3 in Regulating Osteoblast Maturation and Mineralization